TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19610	59053;59054;59055	chr2:178593380;178593379;178593378	chr2:179458107;179458106;179458105
N2AB	17969	54130;54131;54132	chr2:178593380;178593379;178593378	chr2:179458107;179458106;179458105
N2A	17042	51349;51350;51351	chr2:178593380;178593379;178593378	chr2:179458107;179458106;179458105
N2B	10545	31858;31859;31860	chr2:178593380;178593379;178593378	chr2:179458107;179458106;179458105
Novex-1	10670	32233;32234;32235	chr2:178593380;178593379;178593378	chr2:179458107;179458106;179458105
Novex-2	10737	32434;32435;32436	chr2:178593380;178593379;178593378	chr2:179458107;179458106;179458105
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-30
• Domain position: 32
• Structural Position: 35
• Q(SASA): 0.1928
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
I/M	None	None	1.0	D	0.834	0.487	0.518092603711	gnomAD-4.0.0	1.59212E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43324E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
I/A	0.9703	likely_pathogenic	0.9703	pathogenic	-2.491	Highly Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
I/C	0.9809	likely_pathogenic	0.981	pathogenic	-1.776	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
I/D	0.9988	likely_pathogenic	0.9988	pathogenic	-3.244	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	I
I/E	0.9947	likely_pathogenic	0.9949	pathogenic	-3.094	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	I
I/F	0.9171	likely_pathogenic	0.9168	pathogenic	-1.482	Destabilizing	1.0	D	0.846	deleterious	D	0.544945256	None	None	I
I/G	0.9968	likely_pathogenic	0.9969	pathogenic	-2.939	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
I/H	0.9969	likely_pathogenic	0.9968	pathogenic	-2.553	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
I/K	0.9898	likely_pathogenic	0.989	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	I
I/L	0.4849	ambiguous	0.4645	ambiguous	-1.2	Destabilizing	0.993	D	0.417	neutral	N	0.495556788	None	None	I
I/M	0.5959	likely_pathogenic	0.5862	pathogenic	-1.019	Destabilizing	1.0	D	0.834	deleterious	D	0.547480151	None	None	I
I/N	0.9811	likely_pathogenic	0.9803	pathogenic	-2.224	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.559850414	None	None	I
I/P	0.9808	likely_pathogenic	0.9788	pathogenic	-1.614	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	I
I/Q	0.9928	likely_pathogenic	0.9929	pathogenic	-2.166	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
I/R	0.9861	likely_pathogenic	0.9856	pathogenic	-1.626	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
I/S	0.9831	likely_pathogenic	0.9825	pathogenic	-2.731	Highly Destabilizing	1.0	D	0.866	deleterious	D	0.540985691	None	None	I
I/T	0.9622	likely_pathogenic	0.9607	pathogenic	-2.473	Highly Destabilizing	1.0	D	0.858	deleterious	D	0.52304602	None	None	I
I/V	0.0945	likely_benign	0.0969	benign	-1.614	Destabilizing	0.993	D	0.399	neutral	N	0.501514768	None	None	I
I/W	0.9979	likely_pathogenic	0.9978	pathogenic	-2.002	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
I/Y	0.9911	likely_pathogenic	0.9905	pathogenic	-1.79	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.